The objectives of this proposal are (1) to develop methods for quantitating daily exposure to nicotine, tar and carbon monoxide while smoking cigarettes or consuming smokeless tobacco; (2) to apply these methods to study exposure to toxic substances while smoking different numbers or different brands of cigarettes, and (3) to study other factors which are known to influence the intake and effects of tar and nicotine. Assays for quantitating urinary and, if possible, blood concentrations of polycyclic aromatic hydrocarbons, solanesol (a tobacco-specific terpene alcohol), tobacco-specific nitroso compounds and various combustion gases will be developed. Consumption of nicotine will be measured using pharmacokinetic data obtained after intravenous infusion of nicotine in combination with nicotine blood concentration data obtained over 24 hours while smoking in volunteer subjects on a clinical study center, or using casual blood level of nicotine and cotinine in outpatient studies. Using these methods, the effects of smoking different numbers of cigarettes, different tobacco products, i.e., pipes, cigars, snuff and chewing tobacco, and smoking cigarettes with different yields will be studied. In addition, the influence of alcohol and caffeine on nicotine and tar intake, as well as on the metabolism of nicotine and the cardiovascular effects of cigarette smoking, will be studied. Assays developed in our studies will be useful in assessing exposure to toxic components of tobacco smoke in epidemiologic studies and will provide specific information about potential health hazards of different tobacco products. The alcohol and caffeine studies will further our understanding of the influence of these commonly used drugs on smoking behavior and its consequences. Our studies may lead to more effective interventions to reduce the extent and harmful consequences of cigarette smoking.